Studies on the mechanisms of bronchogenic carcinoma induction by chemical and physical factors, alone or in various combinations, are pursued in the hamster respiratory carcinogenesis model. Two recently established Syrian golden hamster colonies (inbred 15:16/EHs:CR and outbred Syrian/CG.FOD) are used for intratracheal instillation of carcinogens adsorbed on particulate carriers alone or in combinations, systemic versus topical treatments, and combined treatments, with carcinogens and cofactors. Respiratory epithelial tissue responses are characterized by histological, ultrastructural, histochemical and biochemical methods, and by their study in organ and cell culture conditions. Light and electron microscopy studies showed that respiratory epithelial of very young hamsters contain a large population of neuroendocrine cells of the APUD type, most frequent in one-day old animals and declining thereafter. Sensitivity to diethylnitrosamine carcinogenesis was higher in newborn hamsters, with high incidences of nasal cavity neoplasms. Submucosal glands in the ethmoid region appear as the site of origin of the malignancies. The regionally selective toxic agents, 3-methylindole and 2-methylnaphthalene, (two components of cigarette smoke with selective toxicity for Clara cells and alveolar type I cells in certain species) have been studied in the hamster model: acute and chronic toxicity levels were determined and found to be different for males and females. Long-term carcinogenicity studies are under way for these agents, also in combinations with other carcinogens. The effects of microtrauma induced by cannulation of the trachea or larynx are studied with or without instillation of saline, particulates and carcinogens; mitotic index measurements show marked epithelial proliferation, mostly of secretory cells.